Anti-inflammatory compositions of aspirin and niacin



United States Patent 3,312,593 ANTI-INFLAMMATORY COMPOSITIONS OF ASPIRIN AND NIACIN Thomas N. Sheen, New York, N.Y., and Earl H. Tiffany,

Jr., Short Hills, and Frank N. Berger, Princeton, N.J., assignors to Carter Products, Inc., New York, N.Y., a corporation of Maryland No Drawing. Filed Mar. 10, 1965, Ser. No. 438,775 3 Claims. (Cl. 167-65) This invention relates to a novel method for systemically treating and controlling inflammation and edema. More particularly, the method of this invention comprises administering internally to one afilicted with an inflammation disorder and/ or edema a therapeutic mixture of aspirin and niacin. Such therapeutic mixture has been found to have unexpected anti-inflammatory activity.

Aspirin (acetylsa-licyclic acid) has been used clinically for many years, mainly for its analgesic and antipyretic properties or to provide compositions having additional beneficial activities.

Niacin (nicotinic acid) has proven of value for the prophylaxis and treatment of pellagra, a vitamin deficiency condition.

It has now been found that the composition of aspirin with niacin gives anti-inflammatory activity entirely unexpected from a consideration of the effects obtained using these components separately or from a consideration of the activities of said components disclosed by the prior art.

In its broad aspect, the present invention relates to the use of aspirin in combination with niacin for the systemic treatment and control of inflammation and edema in warm-blooded animals.

In a more particular aspect of the method, the pharmaceutical composition administered is in suitable oral dosage form and contains from about to about 60 parts by weight of aspirin per part of niacin.

The anti-inflammatory activity of the compositions used in accordance with the instant invention was determined by a modification of the method of La Belle and Tislow described in J. Pharmacol. Exptl. Therap., 98, 19-21, 1950. In the present method, a 1% solution of silver nitrate is injected in the ankle-joint of a significant number of rats. Eighteen'hours later, when a severe inflammation with edema has developed, the test drug, suspended in 1% gum acacia, is given orally. Controls receive only 1% gum acacia.

The foot volume is measured volumetrically prior to the silver nitrate injection, immediately before the administration of the test drug and five hours after said administration. Said measurements are done by means of a suitable calibrated cylinder, modified by cutting otf the open uncalibrated portion. The fluid volume displaced from the cylinder, as read on the graduation, quantitates the edema.

To compute the anti-inflammatory value of the test drug, the volume of the foot prior to the silver nitrate injection is subtracted from the volume of the foot five hours after administration of the drug. The volume differences of the rats in each dose group are summed, averaged and the standard error of the mean calculated.

Table 1, which follows, sets forth the results of the tests. Doses are expressed as milligrams of test drug per kilogram of animal body weight.

3,312,593 Patented Apr. 4, 1967 Standard error 9. 03:0. 96 7. SiO. 62 6. 9i0. 60

silver nitrate induced edema in eleven out of twelve test animals.

Similar tests were made with combinations of niacin with phenacetin. However, the potentiating effect of niacin on aspirin was not obtained with phenacetin eventhough substantially higher doses of niacin than those used in the tabulated tests above were employed.

The ratios in which the therapeutically active components are embodied in the preparations used in accordance with this invention may be varied within rather wide limits. For example, the compositions may contain from about 10 to about 60 parts by Weight of aspirin per part of niacin. Preferred compositions Will contain from about 20 to about 30 parts by weight of aspirin per part of niacin.

The compositions used in accordance with the present invention, in unit dosage form, contain from about 4 to about 15 grains of aspirin and from about 0.06 to about 1.5 grains of niacin. Preferred compositions contain from about 5 to about 10 grains of aspirin and from about 0.16 to about 0.5 grain of niacin.

The compositions administered in accordance with the instant invention can be prepared in any of the standard unit dosage forms. Oral administration by the use of tablets and capsules, or in a liquid form, such as suspensions, solutions or emulsions, is preferred. Said compositions are prepared in a conventional manner by the addition of suitable pharmaceutical carriers including fillers, dilnents, lubricants and the like. When prepared in tablet form, the conventional binding and disintegrating agents are employed.

When aspirin and niacin are the sole active ingredients of the compositions, administered in accordance with the present invention, such compositions possess, in addition to the unexpected anti-inflammatory activity, the analgesic and antipyretic action contributed by the aspirin components. Such additional efiects are extremely beneficial in the treatment of inflammation since pain and fever are usually associated therewith. In addition, the present compositions may contain one or more additional active ingredients compatible With aspirin and niacin, such as appropriate stimulants, sedatives or the like, to add other desirable properties to said compositions. The incorporation of said additives broadens the area of therapeutic utility of the present compositions, making them especially useful in particular cases where, in addition to antiinfiammatory, analgesic and antipyretic activity, other beneficial efiects, such as stimulation, sedation, or the like, are desired.

We claim:

1. A method for systemically treating and controlling inflammation and edema in a warm blooded animal which comprises administering internally to said animal a therapeutic composition comprising, as an essential active ingredient, a pharmaceutically eflective amount of a mixture of aspirin and niacin, the components of said composition being present in a proportion of from about 10 to about 60 parts by weight of aspirin per part of niacin.

2. A method for systemically treating and controlling inflammation and edema in a warm blooded animal which comprises orally administering to said animal a therapeutic dose of a composition containing from about 4 to about 15 grains of aspirin and from about 0.06 to about 1.5 grains of niacin, the components of said composition being present in a proportion of from about 10- to about 60 parts by Weight of aspirin per part of niacin.

3. A method for systemically treating and controlling inflammation and edema in a warm blooded animal which comprises orally administering to said animal a therapeutic dose of a composition containing from about 5 to about 10 grains of aspirin and from about 0.16 to about 0.5 grains of niacin, the components of said composition being present in a proportion of from about 20 to about 30 parts by Weight of aspirin per part of niacin.

References Cited by the Examiner Goodman & Gi lman-The Pharmacological Basis of Therapeutics (1943), pages 224-235 1254-5.

SAM ROSEN, Primary Examiner.

JULIAN S. LEVITT, Examiner.

M. J. COHEN, LEROY B. RANDALL,

, Assistant Examiners.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,512,593 April 4, 1967 Thomas N. Sheen et a1.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

In the heading to the printed specification, line 5, for "Frank N. Berger" read Frank M. Berger column 2, TABLE 1 columns 1 to 3, lines 4 and 5 thereof should appear as shown below instead of as in the patent:

Signed and sealed this 7th day of November 1967.

(SEAL) Attest:

EDWARD J. BRENNER Edward M. Fletcher, Jr.

Commissioner of siatents Attesting Officer 

1. A METHOD FOR SYSTEMICALLY TREATING AND CONTROLLING INFLAMMATION AND EDEMA IN A WARM BLOODED ANIMAL WHICH COMPRISES ADMINISTERING INTERNALLY TO SAID ANIMAL A THERAPEUTIC COMPOSITION COMPRISING, AS AN ESSENTIAL ACTIVE INGREDIENT, A PHARMACEUTICALLY EFFECTIVE AMOUNT OF A MIXTURE OF ASPIRIN AND NIACIN, THE COMPONENTS OF SAID COMPOSITION BEING PRESENT IN A PROPORTION OF FROM ABOUT 10 TO ABOUT 60 PARTS BY WEIGHT OF ASPIRIN PER PART OF NIACIN. 